Defensins at the Interface of Male and Female Innate Immunity

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Gary N CherrIOS-0843649Defensins at the Interface of Male and Female Innate ImmunityThe mammalian female reproductive tract has immune responses to protect against foreign invaders, including the attraction of white blood cells to the area. How sperm cells overcome these defenses as well, and at the same time, play a role in white blood cell attraction, are key questions in reproductive biology. The central hypothesis of this grant seeks to link these two important steps of mammalian reproduction into a unifying concept. The investigators have recently demonstrated that molecules called beta-defensins uniformly coat the entire surface of mammalian sperm during maturation in the male tract. Beta-defensins are key effector peptides of innate immunity found throughout the animal kingdom. These peptides have potent antimicrobial activities and act as chemical attractants. While the expression of beta-defensin peptides by reproductive tissue has been described in several invertebrate species, the presence of beta-defensins on the sperm surface is a novel finding and has only been recently described in mammals. Their presence may reflect adaptations of these peptides for internal fertilization. It is proposed that sperm-associated beta-defensins, which form a uniform surface coat on spermatozoa, promote fertility by first protecting sperm from immunorecognition by the female reproductive tract and then providing enhanced innate immune protection in part by attracting white blood cells. The investigators propose to test these ideas through a combination of in vivo and in vitro experiments using a mouse model. This innovative project will yield answers to longstanding questions in reproductive biology and will provide insights into the sources of variation of reproductive fitness in mammals. The understanding of these mechanisms holds significance for managing reproduction in domestic species, evaluating reproductive fitness in wildlife, and maintaining reproductive health in humans.